1. Field of the Invention
The present invention pertains to a process for the recovery of enantiomers from unwanted mother liquors using racemic mixtures containing stereoisomers having the structure (I) below, or its salt, by heating an enantiomerically enriched chemical mixture with thionyl chloride. 
The present invention is also directed to a process for preparing racemic mixtures containing nearly equal amounts of enantiomers of 2-chlorophenyl glycine methyl ester from mother liquors enriched with unwanted isomers, as its hydrochloride salt, by heating the mother liquors with thionyl chloride.
2. Discussion of Related Art
Racemization is generally carried out by heating an acid with or without the presence of an alkali or a solvent. Free amino acids are difficult to racemize. The temperature required for racemization is often in the range of 140xc2x0-180xc2x0 C. and some decomposition occurs at temperatures within this high range.
Decomposition is extensive with 2-(2-chlorophenyl) glycine, not only because it is difficult to racemize, but also because it easily degrades. 2-(2-chlorophenyl) glycine is an intermediate required in its enantiomerically pure (S) enantiomer for the production of methyl alpha-5 (4,5,6,7-tetrahydro (3,2,-c) thienopyridyl) (2-chlorophenyl)-acetate) to produce an important active pharmaceutical ingredient known as clopidogrel. The enantiomerically pure form of 2-(2-chlorophenyl) glycine is derived from its racemic mixture by optical resolution separation techniques.
The fact that single isomer chiral molecules are known to racemize and revert to optically inactive racemic molecules under adverse conditions is well known in the art. Chemistry and Biochemistry of the Amino Acids, edited by G. C. Barret Chapman and Hall, Chapter Thirteen, deals in some detail with the subject of racemization of amino acids.
U.S. Pat. No. 4,713,470 (the xe2x80x9c""470 patentxe2x80x9d) describes racemization of amino acids carried out by using specially prepared polymers. The racemization process described in the ""470 patent uses an aromatic aldehyde polymer synthesized by reacting an hydroxylaromatic aldehyde with a chloromethylated vinylbenzene polymer under reactive conditions to form an aromatic aldehyde polymer wherein the aldehydic moiety is linked to the polymer through an ether linkage. There is also disclosed a process for the production of the racemization catalyst used therein.
U.S. Pat. No. 4,647,692 (the xe2x80x9c""692 patentxe2x80x9d) is directed to a process for racemization of amino acids by using ketones and organic acids such as acetic acid. Specifically, the ""692 patent discusses a process for resolution of free xcex1-amino acids with in situ racemization. The resolution of 4-hydroxyphenylglycine and 3,4-dihydroxy-phenylglycine with 3-bromocamphor-9-sulphonic acid with in situ racemization is specifically mentioned.
U.S. Pat. No. 4,638,086 (the xe2x80x9c086 patentxe2x80x9d) covers a process for racemization of optically active amino acids that comprises heating amino acids with an effective amount of benzoic or phenylacetic acid or their derivatives which are monosubstituted or polysubstituted on the nucleus by identical or different substituents selected from the group consisting of halogen, lower alkyl, lower alkoxy, hydroxy, acyloxy, and nitro.
U.S. Pat. No 4,237,313 (the xe2x80x9c""313 patentxe2x80x9d) is directed to a process for the racemization of optically active phenylacetic acid derivatives. The process comprises heating an optically active phenylacetic acid derivative to a temperature of at least 150xc2x0 C. in the presence or absence of an inert solvent. None of the above-referenced patents teach a process for the recovery of a racemate of a compound represented by the general structure (I) below from unwanted mother liquors that are rich in one of the enantiomers thereof; 
Compounds obtained by reacting esters of 2-chlorophenylglycine with thienopyridine are useful in the treatment of cardiac conditions and may also be used as anti-platelet agents. U.S. Pat. No. 4,847,265 refers to the (S)+enantiomer of clopidogrel. Other patents such as U.S. Pat. Nos. 4,529,596 and 5,204,469, also refer to methylalpha-5(4,5,6,7-tetrahydro(3,2-c)thienopyridyl)(2-chlorophenyl)-acetate, its isomers and its methods of preparation. U.S. Pat. No. 6,180,793 refers to this compound and also to methods of preparing the required intermediates. These patents refer to the chemical synthesis of racemic (S)(+) or (R)(xe2x88x92) clopidogrel by various methods. In some instances, the resulting clopidogrel is resolved in the end, while in other instances, the resolution step is carried during an intermediate stage.
In each of the aforementioned patents mentioned in the above paragraph, half of the material produced is typically discarded as the unwanted isomer. It may be either in one of the intermediate stages or in the final stage of clopidogrel. For example, the ""793 patent covers synthesis of clopidogrel wherein the resolution step is carried out in any of four different stages in the progression of the synthesis. In any of these steps, the unwanted isomer, representing approximately 50% of the quantity produced, is discarded. Discarding of this material is expensive and contributes to total production cost. It also forms an effluent and increases effluent treatment costs. From an economic viewpoint, it is wasteful to discard an otherwise useful enantiomer from an enantiomerically enriched mixture, such as mother liquors with unwanted isomers. It is preferable to convert these mother liquors into the desired enantiomers via racemization techniques followed by separation of the desired isomer using optical resolution, thereby recovering the required enantiomer from what would otherwise be wasted material.
One aspect of the present invention pertains to a process for the recovery of enantiomers from racemic mixtures containing stereoisomers of compounds having the general formula (I) below 
or its salt by heating an enantiomerically enriched chemical mixture with thionyl chloride.
Another aspect of the present invention includes:
a. Liberating 2-chlorophenyl glycine methyl ester as free base from a concentrated (R)-enantiomer enriched mother liquor, which contains the tartarate or D-camphorsulfonate salt of an unwanted enantiomer;
b. Heating the free base with thionyl chloride so as to effect racemization to form racemized ester hydrochloride;
c. Isolating the racemized ester hydrochloride; and
d. Liberating a racemized ester from the isolated, racemized ester hydrochloride as a further free base from its hydrochloride salt.
The racemized ester may be further processed by conventional resolution steps well known in the art. The present invention thus offers the advantage of recovering a desired enantiomer from unwanted mother liquors that would be otherwise discarded. It further provides an environmental advantage in that chemical waste is reduced.